A new study published in Diabetologia investigated the potential connection between cholesterol crystals (CC) and the diabetic retinopathy (DR) process for earlier diagnosis and less invasive treatments.
Give me some background first.
In DR, reflective deposits of many compositions have been found in the retina correlating with a number of diseases. The study of CC specifically however, has been difficult due to lack of analytical tools.
Now talk about the study.
Investigators used the tissues of human donors, pigs, and mice —observed via scanning electron microscopy (SEM) and immunohistochemistry—to identify CC development and effects.
SEM was performed on retinal tissue and Bruch’s membrane/choroid tissue from the following donors:
- 87 year-old-White male, non-diabetic
- 79-year-old White female, diabetic (10 years duration) with no DR
- 73-year-old White male, insulin dependent diabetic (duration unknown) with proliferative DR (PDR)
Findings?
Utilizing the processed SEM images from these human donors, researchers determined that CCs were discovered in the neural retina of the donor with PDR; none were observed in the non-diabetic donor.
In addition, CCs were identified in the Bruch's membrane of the PDR donor’s choroidal sections, but not in either the control donor or the diabetic donor without retinopathy.
Elemental analysis was performed to determine that the makeup of the crystals were indeed cholesterol as opposed to other chemical compositions.
What about the animal tissue?
Cholesterol levels in the retina were increased in diabetic mice compared to the control mice, while CCs were identified in the retina of pigs that were fed a high-cholesterol diet.
How else did they test CCs ?
The investigators treated Bovine retinal endothelial cells (BREC) and human retinal endothelial cells (HREC) with CCs to observe any potential ramifications.
And…?
They determined that this CC treatment induced pathogenic events consistent with the development of DR. These included:
- Blood–retinal barrier (BRB) breakdown
- Increases in retinal permeability
- Proinflammatory markers increases
- Inflammasome activator increases
Now tell me about treatments.
Diabetic mice were treated with a lipid-sequestering agent for two weeks, resulting in CC removal and a reduction of inflammatory markers.
In addition, fenofibrate was administered to offset detrimental effects during the clinical trials; this was shown to prevent both inflammation and continued retinal permeability.
Expert opinion?
The study authors concluded that, with CCs likely to present in parts of the retina that SEM can’t capture, future clinical trials are necessary to fully understand the role of CCs within the process of DR.
They also suggest that these future trials may help further explore prevention strategies and possible treatment innovation in the future.
Take home.
Per the authors, cholesterol accumulation and CC formation are “a unifying pathogenic mechanism in the development of [DR].” With these highly-reflective crystals visible in retinal imaging, earlier diagnosis and treatment methods may be possible.